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. 2019 Jan 15;12(1):8.
doi: 10.1186/s12920-018-0469-0.

Regulatory network analysis reveals the oncogenesis roles of feed-forward loops and therapeutic target in T-cell acute lymphoblastic leukemia

Mengxuan Xia  1 , Qiong Zhang  1 , Mei Luo  1 , Pan Li  1 , Yingxue Wang  2 , Qian Lei  3 , An-Yuan Guo  4
Affiliations

Regulatory network analysis reveals the oncogenesis roles of feed-forward loops and therapeutic target in T-cell acute lymphoblastic leukemia

Mengxuan Xia et al. BMC Med Genomics. .

Abstract

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Aberrant expressed genes contribute to the development and progression of T-ALL. However, the regulation underlying their aberrant expression remains elusive. Dysregulated expression of transcription factors and miRNAs played important regulatory roles in the pathogenesis of T-ALL.

Methods: In this study, we analyzed the alteration of transcriptome profiling and regulatory networks between T-ALL sample and normal T cell samples at transcriptional and post-transcriptional levels.

Results: Our results demonstrated that genes related to cell cycle and cell proliferation processes were significantly upregulated in T-ALL comparing to normal samples. Meanwhile, regulatory network analyses revealed that FOXM1, MYB, SOX4 and miR-21/19b as core regulators played vital roles in the development of T-ALL. FOXM1-miR-21-5p-CDC25A and MYB/SOX4-miR-19b-3p-RBBP8 were identified as important feed-forward loops involved in the oncogenesis of T-ALL. Drug-specific analyses showed that GSK-J4 may be an effective drug, and CDC25A/CAPN2/MCM2 could serve as potential therapeutic targets for T-ALL.

Conclusions: This study may provide novel insights for the regulatory mechanisms underlying the development of T-ALL and potential therapeutic targets.

Keywords: Cell cycle; Cell proliferation; Feed-forward loops; Pathogenesis; T-ALL.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Differential expression analysis in T-ALL vs normal T-cells. (a) GO enrichment results of upregulated DEGs (red). (b) Venn graph of DEGs in the two comparisons. C: T-ALL Cell lines, N: Normal human T-cells, P: T-ALL patients. Numbers in the sectors are the numbers of DEGs downregulated (green) and upregulated (red). (c) GO enrichment results of downregulated DEGs (green)
Fig. 2
Fig. 2
(a) Hierarchical clustering of miRNAs significantly differentially expressed in the comparisons of T-ALL samples (patients and cell lines) vs normal T cells (b) Hierarchical clustering of TFs. Upregulation in red and downregulation in green
Fig. 3
Fig. 3
The regulatory network of DEGs and DEMs. Green, downregulated genes and miRNAs. Red, upregulated genes and miRNAs. The diamond nodes, TFs; Ellipse nodes, DEMs; Round Rectangle, DEGs. The size of the nodes represents the degree of the nodes
Fig. 4
Fig. 4
TF and miRNA regulatory subnetwork of cell cycle and cell proliferation genes. Light blue Round Rectangle, enriched GO terms; Grey line, regulatory relationship of TFs and miRNAs to genes; Blue line, relationship of mRNAs to GO terms. The means of nodes are the same as Fig. 3
Fig. 5
Fig. 5
FFLs for FOXM1-miR-21-CDC25A and MYB/SOX4-miR-19b-RBBP8 and their enriched GO terms. The means of nodes are the same as Fig. 3
Fig. 6
Fig. 6
GO terms enrichments result for the target genes of miR-21-5p (a) and miR-19b-3p (b)
Fig. 7
Fig. 7
The correlation of drugs IC50 and genes in the regulatory network of FOXM1, MYB, SOX4, miR-21-5p and miR-19b-3p. Drug names are in red font. Upregulation significance genes are red; downregulation significance genes are green. Orange or purple dots mean positive or negative correlation between drugs IC50 and genes expression, respectively
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References

    1. Liu X, Liu S, Chen J, He L, Meng X, Liu S. Baicalein suppresses the proliferation of acute T-lymphoblastic leukemia Jurkat cells by inhibiting the Wnt/β-catenin signaling. Ann Hematol. 2016;95(11):1787–1793. doi: 10.1007/s00277-016-2766-z. - DOI - PubMed
    1. Sanda T, Leong WZ. TAL1 as a master oncogenic transcription factor in T-cell acute lymphoblastic leukemia. Exp Hematol. 2017;53:7–15. doi: 10.1016/j.exphem.2017.06.001. - DOI - PubMed
    1. Durinck K, Goossens S, Peirs S, Wallaert A, Van Loocke W, Matthijssens F, et al. Novel biological insights in T-cell acute lymphoblastic leukemia. Exp Hematol. 2015;43(8):625–639. doi: 10.1016/j.exphem.2015.05.017. - DOI - PubMed
    1. Blank U, Karlsson G, Karlsson S. Signaling pathways governing stem-cell fate. Blood. 2008;111(2):492–503. doi: 10.1182/blood-2007-07-075168. - DOI - PubMed
    1. Collins C, Wang J, Miao H, Bronstein J, Nawer H, Xu T, et al. C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proc Natl Acad Sci U S A. 2014;111(27):9899–9904. doi: 10.1073/pnas.1402238111. - DOI - PMC - PubMed

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